Synthesis and DNA interaction of a mixed proflavine-phenanthroline Troger base

We report the synthesis of an asymmetric Troger base containing the two well characterised DNA binding chromophores. proflavine and phenanthroline. The mode of interaction of the hybrid molecule A as investigated by circular and linear dichroism experiments and a biochemical assay using DNA topoisomerase 1. The data are compatible with a model in which the proflavine moiety intercalates between DNA base pairs and the phenanthroline ring occupies the DNA groove. DNase I cleavage experiments were carried out to investigate the sequence preference of the hybrid ligand and a well resolved footprint was detected at a site encompassing two adjacent 5'-GTC-5-GAC triplets. The sequence preference of the asymmetric molecule is compared to that of the symmetric analogues. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved.